Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China.
BMC Med Genomics. 2023 Jun 19;16(1):141. doi: 10.1186/s12920-023-01581-0.
Polycystic ovary syndrome (PCOS) is often accompanied by increased oxidative stress levels; however, it is still unclear whether PCOS itself is causally related to oxidative stress (OS), whether OS can increase the occurrence of PCOS, and which characteristics of PCOS increase OS levels. Therefore, this study explored the causal relationship between PCOS, its characteristics, and OS.
Two-sample bidirectional and two-sample Mendelian randomisation studies were performed based on publicly available statistics from genome-wide association studies. PCOS; its characteristics, such as testosterone, low-density lipoprotein, high-density lipoprotein; and 11 major OS markers (superoxide dismutase, glutathione S-transferase, glutathione peroxidase, catalase, uric acid, zinc, tocopherol, ascorbic acid, retinol, albumin, and total bilirubin), were studied. The main analytical method used was inverse variance weighting (IVW). Pleiotropy was evaluated using the Mendelian randomisation-Egger intercept. Q and P values were used to assess heterogeneity.
There was no causal relationship between PCOS and the OS indices (all P > 0.05). There was a causal relationship between the OS index, ascorbate level, and PCOS (IVW, odds ratio: 2.112, 95% confidence interval: 1.257-3.549, P = 0.005). In addition, there was a causal relationship between testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, age at menarche, and most OS indices according to the IVW method. The F statistics showed that there was no weak instrumental variable. A sensitivity analysis was performed using the leave-one-out method. No pleiotropy was observed. The results were robust, and the conclusions were reliable.
This study showed for the first time that there was no causal relationship between PCOS and OS. However, there was a causal relationship between the OS index, ascorbate level, and PCOS. It revealed that PCOS itself could not increase OS, and the increase in OS in PCOS was related to other potential factors, such as testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, and age at menarche.
多囊卵巢综合征（PCOS）常伴有氧化应激水平升高；然而，目前尚不清楚 PCOS 本身是否与氧化应激（OS）有因果关系，OS 是否会增加 PCOS 的发生，以及 PCOS 的哪些特征会增加 OS 水平。因此，本研究探讨了 PCOS、其特征与 OS 之间的因果关系。
基于全基因组关联研究中公开的统计数据，进行了两样本双向和两样本孟德尔随机化研究。研究了 PCOS；其特征，如睾酮、低密度脂蛋白、高密度脂蛋白；以及 11 种主要的 OS 标志物（超氧化物歧化酶、谷胱甘肽 S-转移酶、谷胱甘肽过氧化物酶、过氧化氢酶、尿酸、锌、生育酚、抗坏血酸、视黄醇、白蛋白和总胆红素）。主要分析方法为逆方差加权（IVW）。使用 Mendelian 随机化-Egger 截距评估偏倚。Q 和 P 值用于评估异质性。
PCOS 与 OS 指标之间无因果关系（均 P>0.05）。OS 指标、抗坏血酸水平与 PCOS 之间存在因果关系（IVW，比值比：2.112，95%置信区间：1.257-3.549，P=0.005）。此外，根据 IVW 方法，睾酮、低密度脂蛋白、高密度脂蛋白、性激素结合球蛋白、体重指数、三酰甘油、初潮年龄与大多数 OS 指标之间也存在因果关系。F 统计量表明不存在弱工具变量。采用逐一剔除法进行敏感性分析。未观察到偏倚。结果稳健，结论可靠。
本研究首次表明 PCOS 与 OS 之间无因果关系。然而，OS 指标、抗坏血酸水平与 PCOS 之间存在因果关系。这表明 PCOS 本身不能增加 OS，PCOS 中 OS 的增加与其他潜在因素有关，如睾酮、低密度脂蛋白、高密度脂蛋白、性激素结合球蛋白、体重指数、三酰甘油和初潮年龄。
